Testosterone Cypionate Research Articles

Histological ovarian features and hormonal determinations in assigned females at birth transgender individuals according to different testosterone preparations.

Distinct androgen formulations have been used as gender-affirming hormone treatment, but little is known about the specific changes that may occur in the ovary depending on the testosterone preparation used. The study aims to evaluate the histological modifications of the ovarian tissue and the hormonal changes after gender-affirming surgery based on the testosterone preparation employed, such as testosterone cypionate or undecanoate. Unicenter transversal cohort study. Sixty transmasculine persons before and after gender-affirming surgery. A histological examination of the ovaries was conducted, including the follicular population and the characterization of the ovarian stroma. Hormonal status (testosterone, estradiol, FSH, and LH) were also assessed before and after the procedure. The median age of participants was similar between the two groups (27.9 vs. 26.7 years, p = 0.27). There were no differences in all hormonal determinations before gender-affirming surgery between the groups. After surgery, FSH levels increased significantly, especially in the testosterone undecanoate group compared to the cypionate group (72.3 vs. 38.3 U/L, p = 0.02), consistent with LH determinations (43.0 vs. 23.4 U/L, p = 0.02). However, no regimen modification was required for any individual. No statistical differences were observed in any parameter concerning the follicular population, nor were there any variances in the thickness of the tunica albuginea (p = 0.85) or the proportion of luteinized stromal cells. Nevertheless, there was a tendency toward increased luteinization in the testosterone cypionate group (88.2% vs. 76.9%, p > 0.05). In a cohort of transmasculine individuals using different androgen preparations, histological analysis of ovarian tissue revealed comparable findings. Both groups exhibited similar follicular populations and comparable modifications in stromal tissue. However, significant differences were observed in hormonal profiles, although no modification in testosterone dosage was needed.

6590 Androgen Derived Hepatocellular Adenoma And Reinitiation Of Gender Affirming Hormone Therapy

Abstract Disclosure: A.L. McKenna: None. Y. Huang: None. L. Yang: None. N. Loo: None. C. Ritchie: None. A. Metcalfe: None. R. Nakhleh: None. M. Krishna: None. S. Thota-Kammili: None. J. Eleazer: None. A.Y. Chang: None. Hepatocellular adenomas (HCA) are uncommon, benign epithelial tumors of the liver. Risk factors include exogenous estrogen or androgen use, and genetic and metabolic syndromes. Management of HCA is delineated by sex assigned at birth; Observation is recommended in an HCA less than 5 cm in an individual assigned female at birth, while resection of an HCA in an individual assigned male at birth is recommended no matter the size due to risk of malignant transformation. What is not known is whether risk is different for individuals with gender incongruence on gender affirming hormone therapy (GAHT). There is limited data on the risk of HCA in this population. One case report of a transgender man who continued GAHT after diagnosis of an HCA though no follow-up information was available. We present follow-up on a transgender man assigned female at birth with multiple hemorrhagic HCA that was re-initiated on GAHT after stabilization of adenomas off GAHT. Unlike prior cases, the molecular profile showed ß-catenin negative, estrogen and androgen receptors positive. This is the first case report to our knowledge reporting detailed follow-up after restarting masculinizing GAHT after diagnosis of HCA. A 24-year-old transgender man presented to the emergency department with right upper quadrant pain. Initial labs were notable for ALT of 239 units per liter (U/L) and AST 165 U/L. Magnetic resonance imaging (MRI) of the abdomen and liver elastogram revealed multiple bilobar hepatic masses, the largest measuring 9.9 cm concerning for hemorrhagic HCA which was subsequently confirmed on liver biopsy. Immunostains were positive for estrogen and androgen receptors. The patient had no history of alcohol or illicit drug use, tattoos, or family history of liver disease. The patient had been treated with 100 mg of intramuscular testosterone cypionate weekly for the past six years for gender incongruence locally. No testosterone concentrations were available from prior to or during acute presentation. Discontinuation of hormone therapy was recommended along with conservative management with frequent MRI. Over the next 19 months, monitoring revealed improvement/resolution of the auto infarcting adenomas with the last MRI noting two stable HCA measuring 2.1 cm and 0.8 cm without new or enlarging liver lesions. Due to gender dysphoria off GAHT, reinitiation of hormone therapy with low dose AndroGel 1.62% topically was prescribed at 18 months after presentation. The patient has been monitored with labs monthly and plans to obtain MRI abdomen every three months. To date, the patient has tolerated reinitiation of therapy. This case demonstrates that patients on masculinizing GAHT who develop HCA can be conservatively managed and monitored based on pathology and that testosterone does not necessarily explain sex differences in the presentation/malignant transformation of HCA cisgender men as opposed to cisgender women. Presentation: 6/3/2024

6469 Supplement Misadventures: A Case Of Acute Heart Failure, Cardiogenic Shock, And Hormonal Dysregulation Secondary To Surreptitious Use Of Multiple Hormonal Supplements

Abstract Disclosure: K.N. Grennan: None. S. Thota-Kammili: None. A.L. McKenna: None. C.G. Coyle: None. S.L. Samson: None. Introduction: Supplement misuse in the bodybuilding community is prevalent. With the availability of internet ordering and purchasing, patients have access to hormonal supplements without prescription or regulation. Here we present the case of a patient on self-administered hormonal supplements who presented in acute heart failure leading to cardiogenic shock in the setting of concurrent thyroid, adrenal, and gonadal axis dysfunction. Case Description: A 28-year-old male with no significant medical history was transferred to our hospital after presenting to an outside emergency room with dyspnea, cough, nausea, and a subjective fever. He developed acute hypoxic respiratory failure requiring intubation. Echocardiogram performed showed an ejection fraction (EF) of 10%. He was started on two vasopressors and methylprednisolone 1 g daily for two days, due to concern for myocarditis versus giant cell arteritis. Hormonal work-up showed TSH 0.02 mIU/L (normal range 0.3-4.2), free T4 0.4 ng/dL (0.9-1.7), total T3 48 ng/dL (80-200), FSH <0.3 IU/L (1.2-15.8), LH <0.2 IU/L (1.3-9.6), ACTH <5.0 pg/mL (7.2-63), cortisol 1.7 mcg/dL (2.5-12), estradiol 171 pg/mL (8.0-35), total testosterone 1730 ng/dL (240-950), and prolactin 47 ng/mL (4.0-15.2). He received 10 mg dexamethasone at the outside facility. A medication bag found by his family included online purchases of non-prescribed testosterone cypionate and enanthate, liothyronine, anastrozole, and clomiphene. None were medical grade. He was also taking the anabolic steroid clenbuterol for 3 days prior. Echocardiogram on day 3 of admission showed an improved EF of 36%. Cardiac magnetic resonance imaging (MRI) showed a papillary fibroelastoma and myocarditis. Patient was weaned off vasopressors and the ventilator. He was discharged on levothyroxine 50 mcg daily and hydrocortisone 10 mg twice daily for outpatient reassessment. Transesophageal echocardiogram confirmed diagnosis of papillary fibroelastoma. One month Endocrinology clinic follow-up showed no evidence of posterior pituitary, thyroid, or adrenal axis dysfunction or growth hormone excess, but he continued to have gonadal axis suppression with elevated prolactin and estradiol, the latter thought to be secondary to conversion from testosterone. Pituitary MRI showed no micro or macroadenoma. His EF recovered to 50%. He is pending surgical removal of the aortic valve fibroelastoma. Discussion: With hormonal supplements easily accessible online, it is important for physicians to counsel patients about the dangers of misuse. This case highlights a previously healthy 28-year-old man who presented in critical condition with cardiogenic shock and hypothalamic-pituitary axis dysfunction from supplements he purchased online. There should be targeted educational interventions regarding the harm of supplements aimed at the bodybuilding community to prevent similar cases. Presentation: 6/2/2024

7019 Persistently Elevated Estradiol Levels in a Transgender Male; An Unexpected Pregnancy

Abstract Disclosure: M. Kanin: None. S. Grock: None. N. Agrawal: None. Background: Testosterone is the backbone of gender-affirming hormone therapy (GAHT) for transmasculine and non-binary individuals assigned female at birth (AFAB). While testosterone can affect fertility, it should not be used as contraception and is contraindicated in pregnancy. It is important to counsel patients on fertility preservation, pregnancy, and contraceptive options prior to testosterone initiation. However, the Endocrine Society Guidelines and World Professional Association for Transgender Health Standards of Care provide minimal guidance on reproductive health and contraceptive options. Case Description: An 18-year-old individual AFAB on GAHT with testosterone was referred to endocrinology for elevated estradiol levels. On presentation, the patient denied vaginal bleeding or breast tenderness. The date of last menstrual period was reported as two years prior. There was no significant past medical or surgical history. Medications included subcutaneous testosterone cypionate 20 mg weekly. Physical exam was notable for elevated BMI 42.6kg/m², mild facial hair and central adiposity. Hormone analysis revealed testosterone of 172 ng/dL (adult male: 200-1000) and estradiol 27,322 pg/mL (mid-cycle Female: 80-400). Estradiol by mass spectrometry obtained due to concern for immunoassay interference resulted at > 10,000 pg/mL. FSH <0.1 mIU/mL, LH<0.1 mIU/mL, DHEA-S 2,460 ng/mL (adult female: 400-3600), androstenedione 1.85 ng/mL (0.260 - 2.140), prolactin 328 ng/mL (3 -23.1). CT abdomen and pelvis and pituitary MRI were ordered to assess for ovarian, adrenal and/or pituitary tumor. Later that day additional laboratory tests revealed alpha fetoprotein 126 ng/mL (0 -6.7), progesterone 100.2 ng/mL (luteal phase: 3.0-25.0), beta-hCG 32,571 mIU/ml, inhibin B<10, inhibin A 500.1pg/ml (luteal phase: 40-80) and CA-125 19 U/mL (0 - 35). Given the elevated beta-hcg the patient was asked if they were having sex in a way that could result in pregnancy to which they answered affirmatively. CT and MRI were cancelled, and abdominal ultrasound was obtained which revealed a single living intrauterine pregnancy with estimated gestational age 35 weeks 2 days. Testosterone was stopped and they subsequently delivered a healthy baby girl. Conclusion: Gender diverse patients on testosterone can experience unplanned pregnancy. As testosterone is contraindicated in pregnancy, counseling on reproductive health and contraception is needed. A pregnancy test should be considered prior to initiating hormones for appropriate individuals. It is important to be aware that Individuals AFAB may not desire estrogen containing birth control and placement of intrauterine devices can be dysphoric. Further investigation into how contraceptive options may affect outcomes for individuals on GAHT is needed to minimize barriers to care and to enable patients to make well informed decisions. Presentation: 6/2/2024

8125 Long-term Effects of Gender Affirming Hormone Therapy (GAHT) on Lipid Profile

Abstract Disclosure: G. Le: None. S. Pinkson: None. J. Trejo: None. D. Tripathy: None. Long-term Effects of Gender Affirming Hormone Therapy (GAHT) on Lipid Profile There is differential effect of long-term Estrogen and Testosterone therapy on lipid profile. While oral estradiol therapy in post-menopausal women has been associated with increased serum triglyceride and HDL, testosterone therapy in hypogonadal men decreases total cholesterol, LDL and HDL cholesterol. However, the long-term effects of Estrogen and Testosterone on lipid profile in transgender patients are not clear. We conducted a retrospective study to analyze the long-term effects of GAHT in transgender men and women followed in Endocrinology Clinic at Veterans Affairs Hospital. 36 transgender men (age 38 ± 2 years, on IM Testosterone cypionate) and 54 transgender women (age 46 ± 2 years, 36 on E2 tablet, 12 on patch, 6 on IM) were followed for 46 ± 5 months and 61 ± 5 months, respectively. Total cholesterol, triglyceride, HDL, LDL cholesterol, systolic and diastolic blood pressures, and BMI were compared before and after initiation of therapy. As expected, following GAHT, total testosterone was higher (546 ± 48 vs. 35 ± 9 ng/dL, P<0.001) in transgender men; in transgender women, serum E2 was higher (110 ± 9 vs. 26 ± 2 pg/dL, P<0.001) and total testosterone was suppressed (444 ± 29 ng/dL vs. 66 ± 13 ng/dL). In transgender men, after a follow-up period of approximately 4 years, there were no significant changes in lipid profile (total cholesterol 178 ± 8 vs. 175 ± 8 mg/dL, triglyceride 121 ± 4 vs 134 ± 12 mg/dL, HDL 47 ± 2 vs. 44 ± 2 mg/dL, LDL 107 ± 7 vs. 106 ± 8 mg/dL, all p=NS). Similarly in transgender women, no difference in lipid profile (total cholesterol 170 ± 5 vs. 175 ± 4 mg/dL, triglyceride 118 ± 7 vs 140 ± 9 mg/dL, HDL 49 ± 2 vs. 53 ± 3 mg/dL, LDL 99 ± 4 vs. 97 ± 4 mg/dL, all p=NS) was observed after 5 years of GAHT. There were no differences in lipid profile regardless of E2 tablet, patch or IM therapy. In transgender men, there was an increase in diastolic blood pressure (72 ± 3 vs. 76 ± 2 mmHg, P<0.05) while in transgender women there was decrease in systolic blood pressure (124 ± 2 vs. 118 ± 2 mmHg, p<0.005), and slight increase in BMI (28 ± 0.9 vs. 30 ± 1 kg.m2, P<0.005). In conclusion, long-term testosterone therapy in transgender men and estrogen therapy in transgender women was not associated with worsening lipid profile. Estrogen therapy was associated with lower BP in transgender women and testosterone therapy led to higher BP in transgender men. Presentation: 6/2/2024

7019 Persistently Elevated Estradiol Levels in a Transgender Male; An Unexpected Pregnancy

Abstract Disclosure: M. Kanin: None. S. Grock: None. N. Agrawal: None. Background: Testosterone is the backbone of gender-affirming hormone therapy (GAHT) for transmasculine and non-binary individuals assigned female at birth (AFAB). While testosterone can affect fertility, it should not be used as contraception and is contraindicated in pregnancy. It is important to counsel patients on fertility preservation, pregnancy, and contraceptive options prior to testosterone initiation. However, the Endocrine Society Guidelines and World Professional Association for Transgender Health Standards of Care provide minimal guidance on reproductive health and contraceptive options. Case Description: An 18-year-old individual AFAB on GAHT with testosterone was referred to endocrinology for elevated estradiol levels. On presentation, the patient denied vaginal bleeding or breast tenderness. The date of last menstrual period was reported as two years prior. There was no significant past medical or surgical history. Medications included subcutaneous testosterone cypionate 20 mg weekly. Physical exam was notable for elevated BMI 42.6kg/m², mild facial hair and central adiposity. Hormone analysis revealed testosterone of 172 ng/dL (adult male: 200-1000) and estradiol 27,322 pg/mL (mid-cycle Female: 80-400). Estradiol by mass spectrometry obtained due to concern for immunoassay interference resulted at > 10,000 pg/mL. FSH <0.1 mIU/mL, LH<0.1 mIU/mL, DHEA-S 2,460 ng/mL (adult female: 400-3600), androstenedione 1.85 ng/mL (0.260 - 2.140), prolactin 328 ng/mL (3 -23.1). CT abdomen and pelvis and pituitary MRI were ordered to assess for ovarian, adrenal and/or pituitary tumor. Later that day additional laboratory tests revealed alpha fetoprotein 126 ng/mL (0 -6.7), progesterone 100.2 ng/mL (luteal phase: 3.0-25.0), beta-hCG 32,571 mIU/ml, inhibin B<10, inhibin A 500.1pg/ml (luteal phase: 40-80) and CA-125 19 U/mL (0 - 35). Given the elevated beta-hcg the patient was asked if they were having sex in a way that could result in pregnancy to which they answered affirmatively. CT and MRI were cancelled, and abdominal ultrasound was obtained which revealed a single living intrauterine pregnancy with estimated gestational age 35 weeks 2 days. Testosterone was stopped and they subsequently delivered a healthy baby girl. Conclusion: Gender diverse patients on testosterone can experience unplanned pregnancy. As testosterone is contraindicated in pregnancy, counseling on reproductive health and contraception is needed. A pregnancy test should be considered prior to initiating hormones for appropriate individuals. It is important to be aware that Individuals AFAB may not desire estrogen containing birth control and placement of intrauterine devices can be dysphoric. Further investigation into how contraceptive options may affect outcomes for individuals on GAHT is needed to minimize barriers to care and to enable patients to make well informed decisions. Presentation: 6/2/2024

8125 Long-term Effects of Gender Affirming Hormone Therapy (GAHT) on Lipid Profile

Abstract Disclosure: G. Le: None. S. Pinkson: None. J. Trejo: None. D. Tripathy: None. There is differential effect of long-term Estrogen and Testosterone therapy on lipid profile. While oral estradiol therapy in post-menopausal women has been associated with increased serum triglyceride and HDL, testosterone therapy in hypogonadal men decreases total cholesterol, LDL and HDL cholesterol. However, the long-term effects of Estrogen and Testosterone on lipid profile in transgender patients are not clear. We conducted a retrospective study to analyze the long-term effects of GAHT in transgender men and women followed in Endocrinology Clinic at Veterans Affairs Hospital. 36 transgender men (age 38 ± 2 years, on IM Testosterone cypionate) and 54 transgender women (age 46 ± 2 years, 36 on E2 tablet, 12 on patch, 6 on IM) were followed for 46 ± 5 months and 61 ± 5 months, respectively. Total cholesterol, triglyceride, HDL, LDL cholesterol, systolic and diastolic blood pressures, and BMI were compared before and after initiation of therapy. As expected, following GAHT, total testosterone was higher (546 ± 48 vs. 35 ± 9 ng/dL, P<0.001) in transgender men; in transgender women, serum E2 was higher (110 ± 9 vs. 26 ± 2 pg/dL, P<0.001) and total testosterone was suppressed (444 ± 29 ng/dL vs. 66 ± 13 ng/dL). In transgender men, after a follow-up period of approximately 4 years, there were no significant changes in lipid profile (total cholesterol 178 ± 8 vs. 175 ± 8 mg/dL, triglyceride 121 ± 4 vs 134 ± 12 mg/dL, HDL 47 ± 2 vs. 44 ± 2 mg/dL, LDL 107 ± 7 vs. 106 ± 8 mg/dL, all p=NS). Similarly in transgender women, no difference in lipid profile (total cholesterol 170 ± 5 vs. 175 ± 4 mg/dL, triglyceride 118 ± 7 vs 140 ± 9 mg/dL, HDL 49 ± 2 vs. 53 ± 3 mg/dL, LDL 99 ± 4 vs. 97 ± 4 mg/dL, all p=NS) was observed after 5 years of GAHT. There were no differences in lipid profile regardless of E2 tablet, patch or IM therapy. In transgender men, there was an increase in diastolic blood pressure (72 ± 3 vs. 76 ± 2 mmHg, P<0.05) while in transgender women there was decrease in systolic blood pressure (124 ± 2 vs. 118 ± 2 mmHg, p<0.005), and slight increase in BMI (28 ± 0.9 vs. 30 ± 1 kg.m2, P<0.005). In conclusion, long-term testosterone therapy in transgender men and estrogen therapy in transgender women was not associated with worsening lipid profile. Estrogen therapy was associated with lower BP in transgender women and testosterone therapy led to higher BP in transgender men. Presentation: 6/2/2024

Effects of androgenic modulation on the morphophysiology of the adrenal cortex of male gerbils

The study aimed to investigate the repercussions of androgen modulation on the adrenal cortex of male gerbils, focusing on the morphophysiology, proliferation, and cell death, as well as the expression of hormone receptors and steroidogenic enzymes. Mongolian gerbils (Meriones unguiculatus) were divided into three experimental groups: Control (C), Testosterone (T), animals received injections of testosterone cypionate and Castrated (Ct), animals underwent orchiectomy. The results showed that castration increased the zona fasciculata and promoted cell hypertrophy in all zones. Testosterone supplementation increased cell proliferation and cell death. Androgen modulation promoted an increase in AR, Erα, and ERβ. Castration promoted an increase in the CYP19, while decreasing 17βHSD enzymes. Testosterone supplementation, on the other hand, reduced CYP17 and increased CYP19 and 3βHSD enzymes. By analyzing the effects of androgen supplementation and deprivation, it can be concluded that testosterone is responsible for tissue remodeling in the cortex, regulating the rate of cell proliferation and death, as well as cell hypertrophy. Testosterone also modulate steroid hormone receptors and steroidogenic enzymes, consequently affecting the regulation, hormone synthesis and homeostasis of this endocrine gland.

Effects of a supraphysiological dose of testosterone cypionate on salivary gland function in adult male Wistar rats

The abusive use of anabolic androgenic steroids has become a serious health problem worldwide, but its effects on oral health are still poorly understood. Therefore, the objective of this study was to evaluate the effects of a supraphysiological dose of testosterone cypionate (TC) on salivary biochemical, histomorphology, immunohistochemistry, and redox state parameters of parotid and submandibular glands. Twenty male Wistar rats, 12 weeks old, were divided into two groups (n=10/group): a control group and TC group, which received a dose of 20 mg/kg, once a week, for 6 weeks. Post treatment, the saliva and glands were collected. A supraphysiological dose of TC increased plasma and salivary testosterone concentrations. Although TC did not alter salivary flow, pH, and buffering capacity, the treatment increased the salivary secretion of total protein and reduced amylase, calcium, phosphate, and potassium. TC reduced the connective tissue area in the parotid gland and acinar area of the submandibular gland, while increasing the granular convoluted tubule area in the submandibular gland. Proliferating cell nuclear antigen was higher in the acinar cells of the submandibular glands from the TC group. Moreover, TC increased concentrations of total oxidant capacity and damaged lipids in both salivary glands, while total antioxidant activity and uric acid were lower in the submandibular gland, and reduced glutathione was higher in both glands. Superoxide dismutase, catalase, and glutathione peroxidase activities were higher in the parotid gland, while only glutathione peroxidase activity was lower in the submandibular gland of the TC group. In conclusion, TC abuse may be a potential factor for dysfunction of the parotid and submandibular glands, becoming a risk factor for the oral and systemic health of users.

Testosterone Promotes Nerve Tethering and Acellular Biomaterial Perineural Fibrosis in a Rat Wound Repair Model.

Objective: Nerve scarring after traumatic or iatrogenic exposure can lead to impaired function and pain. Nerve-adjacent biomaterials promoting a regenerative tissue response may help reduce perineural fibrosis. Our prior work suggests that testosterone may promote fibrotic skin scarring, but it is unknown how testosterone alters nerve fibrosis or shifts the response to biomaterials. Approach: Sterilized Lewis rats received either testosterone cypionate (+T) or placebo (-T) biweekly. Fifteen days later, wounds were created over the sciatic nerve and covered with an acellular matrix (AM) or closed via primary closure (PC). At day 42, force gauge testing measured the force required to mobilize the nerve, and wound tissue was analyzed. Results: Nerve mobilization force was greater in +T versus -T wounds (p < 0.01). Nerves tore before gliding in 60% of +T versus 6% of -T rats. Epidermal gap (p < 0.01), scar width (p < 0.01), and cross-sectional scar tissue area (p = 0.02) were greater in +T versus -T rats. +T versus -T rats expressed less Col-3 (p = 0.02) and CD68 (p = 0.02). Nerve mobilization force trended nonsignificantly higher for PC versus AM wounds and for +T versus -T wounds within the AM cohort. Innovation: Testosterone increases nerve tethering in the wound healing milieu, altering repair and immune cell balances. Conclusion: Testosterone significantly increases the force required to mobilize nerves in wound beds and elevates histological markers of scarring, suggesting that testosterone-induced inflammation may increase perineural adhesion. Testosterone may reduce the potential anti-tethering protective effect of AM. Androgen receptor antagonism may represent a therapeutic target to reduce scar-related nerve morbidity.

Blood-based markers of differential efficacy of bipolar androgen therapy and enzalutamide in the randomized TRANSFORMER trial.

LBA5014 Background: Bipolar androgen therapy (BAT) for metastatic castration-resistant prostate cancer (mCRPC) is administered by alternating between supraphysiologic and near-castrate serum testosterone levels through intramuscular administration of testosterone cypionate 400mg given every 28 days together with ongoing androgen suppression. BAT is effective in a subset of patients, but evidence for predictive treatment selection is lacking. The goal of the study is to determine whether blood-based markers can be identified in the TRANSFORMER study, a randomized trial of abiraterone-pretreated mCRPC patients assigned to BAT or enzalutamide (Enza). Methods: We conducted whole genome and whole exome sequencing of circulating tumor DNA samples collected from the TRANSFORMER study. In this post-hoc biomarker study of a randomized trial, we sought to identify markers that predict preferential benefit from BAT or Enza in mCRPC patients progressing on abiraterone. We compared clinical or radiographic progression-free survival (PFS) and overall survival (OS) between BAT and Enza arms in subgroups defined by biomarker status and estimated treatment effects via the Cox regression model, stratified by duration of prior abiraterone treatment. To determine whether a molecular event is a predictive biomarker, we tested the interaction term of the dichotomized marker status by treatment arms. Statistical tests were two-sided, and p values ≤ 0.05 were deemed to indicate statistical significance. Results: We focused on somatic alterations implicated in androgen receptor (AR) signaling that can be detected at a relatively high frequency in blood samples. Whole genome sequencing and whole exome sequencing of cell-free DNA from 62 patients revealed tumor-specific AR pathway alterations, including AR point mutations and amplifications (33/62, 53.2%). In men with positive AR alterations detected in blood, BAT was more efficacious than Enza (median PFS 4.2 months vs. 2.9 months; hazard ratio [HR] 0.59[95% CI 0.25-1.37], P=0.22), while Enza was superior to BAT in those without AR alterations (median PFS 8.4 months vs. 3 months; HR 3.62[95%CI 1.44-9.1], P=0.006). We detected a significant interaction between AR alteration status and treatment types using PFS as the endpoint ( Pinteraction=0.002). The differential benefit is upheld with OS as the endpoint ( Pinteraction &lt;0.001). In men with positive AR alterations, OS was longer with BAT compared with Enza (median OS 29.6 months vs. 24.1 months; HR 0.41[95% CI 0.16-1.03], P=0.058). In contrast, in men without AR alterations, OS was worse with BAT compared with Enza (median OS 19.3 months vs. NR; HR 4.38[95% CI 1.21-15.89], P=0.025). Conclusions: Metastatic CRPC patients progressing on abiraterone with AR alterations detected in blood may benefit preferentially from BAT. Routine liquid biopsy testing may enable further adoption of BAT.

Effect-directed analysis of androgenic compounds from sewage sludges in China

The safety of municipal sewage sludge has raised great concerns because of the accumulation of large-scale endocrine disrupting chemicals in the sludge during wastewater treatment. The presence of contaminants in sludge can cause secondary pollution owing to inappropriate disposal mechanisms, posing potential risks to the environment and human health. Effect-directed analysis (EDA), involving an androgen receptor (AR) reporter gene bioassay, fractionation, and suspect and nontarget chemical analysis, were applied to identify causal AR agonists in sludge; 20 of the 30 sludge extracts exhibited significant androgenic activity. Among these, the extracts from Yinchuan, Kunming, and Shijiazhuang, which held the most polluted AR agonistic activities were prepared for extensive EDA, with the dihydrotestosterone (DHT)-equivalency of 2.5 – 4.5 ng DHT/g of sludge. Seven androgens, namely boldione, androstenedione, testosterone, megestrol, progesterone, and testosterone isocaproate, were identified in these strongest sludges together, along with testosterone cypionate, first reported in sludge media. These identified androgens together accounted for 55 %, 87 %, and 52 % of the effects on the sludge from Yinchuan, Shijiazhuang, and Kunming, respectively. This study elucidates the causative androgenic compounds in sewage sludge and provides a valuable reference for monitoring and managing androgens in wastewater treatment.

Supraphysiologic Testosterone Administration Impairs Late Osseointegration in Male Rats.

To evaluate the effect of supraphysiologic administration of testosterone in an early and late model of implant osseointegration in rat tibiae. A total of 40 rats were randomly allocated into four groups (n = 10/ group), which were divided according to the type of experiment and time of osseointegration: (1) vehicle (14 days), (2) testosterone (14 days), (3) vehicle (42 days), and (4) testosterone (42 days). Testosterone cypionate (7.5 mg/kg) administration started 4 weeks before implant placement, and the injections were performed daily until euthanasia. Machined-surface titanium implants (2.2 mm in diameter and 4 mm high) were placed bilaterally in the tibia of animals 28 days after the first testosterone injection. At days 14 and 42 after implant placement, euthanasia was performed and the tibiae were harvested to perform biomechanical evaluation and histomorphometric analysis of bone-to-implant contact (BIC%) and bone between the threads (BBT%). There was no statistical difference in the removal torque of the implants between the groups treated with the vehicle (control group) or testosterone (P > .05). At 14 days of osseointegration, the BIC% and BBT% did not differ between vehicle or testosterone groups (P > .05), while at 42 days, both the BIC% and BBT% were significantly reduced by testosterone compared to the vehicle group (P < .05). Testosterone cypionate in supraphysiologic dose impaired late-phase osseointegration in rat tibiae.

Quality of life and level of satisfaction with pharmacotherapeutic follow-up in a transgender health center in Brazil

Trans people face numerous barriers to access and permanence in health services, which makes it difficult, among other things, to know about their quality of life and satisfaction with health services related to these users. Thus, the objective was to describle the quality of life and satisfaction with pharmacotherapeutic follow-up in transgender people. A cross-sectional, descriptive, and quantitative study was conducted between January and September 2022 at a specialized outpatient clinic for transgender individuals. The following aspects were describle: sociodemographic and medication profiles; quality of Life, which was measured using the WHOQOL-BREF questionnaire; and levels of satisfaction with Pharmacotherapeutic Monitoring, assessed through the Pharmacy Services Satisfaction Questionnaire (QSSF). Descriptive analyses employed measures of central tendency, absolute and relative frequencies, while inferential analyses used the Student’s t test. A total of 101 transgender individuals participated in the study, with a mean age of 25 years, the majority being single (79.2%/80), having more than 11 years of education (47.5%/n = 48), and comprising 48.5% (n = 49) transgender women. Hormone use was reported by 59.4% (n = 60) of the participants, with 18.3% (n = 11) of self-medication. Testosterone cypionate was the most common hormone used by transgender men (84%), while cyproterone acetate and estradiol represented 60.4% of hormone use among transgender women. Additionally, 36 transgender individuals were taking other drugs (n = 60), mainly antidepressives (28%). The WHOQOL-BREF showed higher scores in the domains of self-rated Quality of Life, and physical, and psychological well-being among transgender women compared to transgender men, but without statistical differences. Income revealed a statistically significant association with psychological domains and overall quality of life. The results of the QSSF indicated that the overall mean and average scores per question were higher than 4, suggesting that 100% of the sample was satisfied with the provided service. No statistically significant differences were observed in the Quality of Life between transgender men and women, but income was associated with the psychological domain and overall Quality of Life. All participants reported satisfaction with the Pharmacotherapeutic Monitoring service; however, there is a need to expand service offerings, such as medication dispensing.

Bipolar androgen therapy plus nivolumab for patients with metastatic castration-resistant prostate cancer: the COMBAT phase II trial

Cyclic high-dose testosterone administration, known as bipolar androgen therapy (BAT), is a treatment strategy for patients with metastatic castration-resistant prostate cancer (mCRPC). Here, we report the results of a multicenter, single arm Phase 2 study (NCT03554317) enrolling 45 patients with heavily pretreated mCRPC who received BAT (testosterone cypionate, 400 mg intramuscularly every 28 days) with the addition of nivolumab (480 mg intravenously every 28 days) following three cycles of BAT monotherapy. The primary endpoint of a confirmed PSA50 response rate was met and estimated at 40% (N = 18/45, 95% CI: 25.7–55.7%, P = 0.02 one-sided against the 25% null hypothesis). Sixteen of the PSA50 responses were achieved before the addition of nivolumab. Secondary endpoints included objective response rate (ORR), median PSA progression-free survival, radiographic progression-free survival (rPFS), overall survival (OS), and safety/tolerability. The ORR was 24% (N = 10/42). Three of the objective responses occurred following the addition of nivolumab. After a median follow-up of 17.9 months, the median rPFS was 5.6 (95% CI: 5.4–6.8) months, and median OS was 24.4 (95% CI: 17.6–31.1) months. BAT/nivolumab was well tolerated, resulting in only five (11%) drug related, grade-3 adverse events. In a predefined exploratory analysis, clinical response rates correlated with increased baseline levels of intratumoral PD-1 + T cells. In paired metastatic tumor biopsies, BAT induced pro-inflammatory gene expression changes that were restricted to patients achieving a clinical response. These data suggest that BAT may augment antitumor immune responses that are further potentiated by immune checkpoint blockade.

The Lipid Solubility of Most Drugs Play Important Role of Its Pharmacological Action and Duration of Action

The fact of human body and animal body formed of organs which formed of tissue which its constituents are the cells. The cell enveloped by cell membrane which contain more its content of lipid compounds to protect the cell. Hence when the chemical compounds (drugs) across to the cytoplasm of the cell must have a lipophilic character. Also there is a fact the oily substances not mix with the watery substance, so must be take a cream form (water in oil or oil in water emulsion), so the drugs must be soluble in lipid to across the cell to obtain the desirable effect. The partition co-efficient is a significant expression of lipid solubility. Many of drugs convert to prodrug this prodrug has highly lipid solubility and has long duration of action e.g., testosterone cypionate, rolitetracycline, penicillin procaine, benzylpenicillin G, nandrolone decanoate….etc., on the other hand the water soluble compounds (hydrophilic drugs) e.g., vitamin B complexes which exert its effects and excreted from the kidney quickly this indicate to no long duration of vitamin B complex except the cyanocobalamin (vit.B12) which incorporated to sesame oil to deposit in the body to treatment the inflammation of nerves of diabetic patients which suffering from neuropathy.

Abstract B039: Effect of cross-sex testosterone therapy on Pik3ca-driven breast cancer incidence in mice

Abstract Background: The majority of transmasculine individuals—assigned female at birth—pursue gender-affirming testosterone therapy (TT) to treat their gender dysphoria. It remains unknown the extent to which TT modulates the breast, including breast cancer (BC) risk, in transmasculine individuals. Given that hormone regulation of breast development is similar in mice and humans, mouse models are an excellent methodology to understand the effect of TT on BC development. We used a BC mouse model, MMTV-Cre Pik3caf/wt, to investigate the effect of testosterone on estrogen receptor positive (ER+) BC development. Method: Immunohistochemistry confirmed that our MMTV-Cre Pik3caf/wt tumors are ER+. We established 5 study arms: female controls (n=4), oophorectomized female controls (n=6), male mice (n=5), female mice receiving weekly 400 µg s.c. of testosterone cypionate (n=5), and oophorectomized female mice receiving weekly testosterone cypionate (n=5). Mammary tumor development was monitored weekly; palpable tumors were measured 3x a week. Mice were euthanized when their largest tumor reached 1cm, or if multiple tumors arise, when the combined tumor burden reaches 2 cm. Mice that have not reached endpoint by 48 weeks of age were euthanized and censored. The total number of tumors were observed during necropsy. Results: All 4 female controls developed a mean of 4 tumors each and were euthanized at around 35 weeks as the largest tumor reached 1 cm. The remaining mice were euthanized study endpoint of 48 weeks. Only 1 of 5 female mice receiving testosterone had a macroscopic tumor at 48 weeks. Hence, the total number of tumors developed among female mice receiving testosterone are similar or lower than female controls. Three out of 6 of oophorectomized females developed an average of 2 tumors while 2 of 5 female oophorectomized mice receiving testosterone developed 3 tumors each. Thus, when compared to intact females, oophorectomy appears to increase the lag time to Pik3ca tumor development. Lastly, 1 of 5 male mice developed 4 tumors. Conclusion: This pilot study demonstrated that testosterone does not increase ER+ BC incidence in Pik3ca-transgenic mice. Findings in oophorectomized mice suggest that aromatization of testosterone to estradiol may not contribute significantly to tumor development in these mice. Our findings provides insights into about BC risk associated with TT in transmasculine individuals. More studies are warranted to understand the health effects of gender-affirming hormone therapy, and reduce healthcare disparities in the transgender community. Citation Format: Lin Wang, Abhishek Thavamani, Erica S. Massicott, Vanessa C. Bret-Mounet, Joseph Abirached, John G. Clohessy, Gabrielle M. Baker, Gerburg M. Wulf, Yujing Jan Heng. Effect of cross-sex testosterone therapy on Pik3ca-driven breast cancer incidence in mice [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B039.

FRI323 Prolactinoma Recurrence With Testosterone Treatment In Transgender Male

Abstract Disclosure: N. Arnouk: None. P.R. Schroeder: None. Introduction: We present a case of recurrent hyperprolactinemia due to testosterone treatment for gender-affirming hormonal therapy in a transgender male after being controlled on cabergoline for more than a year. Case: A 27-year-old female with history of HTN and polycystic ovary syndrome was diagnosed with pituitary microadenoma after hospital admission for headache and blurry vision. MRI brain showed a mass in the sella and right parasella measuring 36 mm W x 36 mm D x 44 mm H. Hormonal workup showed prolactin (PRL) &amp;gt;999 ng/mL in the diluted assay. The patient was treated medically with cabergoline and discharged home. PRL level improved to 22 ng/mL on treatment. Cabergoline was continued at 0.5 mg twice weekly. The patient was lost to follow-up but returned to clinic after 8 months with PRL level of 58 ng/mL. Cabergoline 0.5 mg twice weekly was continued. PRL level monitoring every ∼6 weeks showed an increase to 184 ng/mL and then 199 ng/mL. Cabergoline was increased to 1 mg twice weekly. PRL level 1 month later was 222 ng/mL. Repeat brain MRI showed markedly decreased microadenoma 4.8 X 2.6 mm. The patient was asymptomatic with no headache, blurry vision, or galactorrhea. On further questioning, the patient reported starting transgender female to male testosterone cypionate 200 mg/mL once weekly for the past 6 months. After discussion with the primary care provider who was managing testosterone treatment, he was started on 60 mg weekly, and the dose was gradually increased to 80 mg weekly to stop the menstrual period. With the 60-mg weekly cypionate dose, the testosterone level was 346 pg/mL, and PRL level was 184 ng/mL. With the cypionate dose of 80 mg weekly, PRL increased to 194 ng/mL and 222 ng/mL. The cypionate dose was decreased to 60 mg weekly, based on literature noting elevated PRL level with testosterone replacement in patients with prolactinoma and hypogonadism. Based on repeat blood work showing elevated testosterone 366 pg/mL with PRL 318 ng/mL, the plan is to start an aromatase inhibitor. Discussion: Testosterone treatment as hormonal affirming therapy in some transgender female to male patients may exacerbate pre-existing hyperprolactinemia or induce PRL secretion, thus close monitoring is required. Testosterone is aromatized to estradiol, which then stimulates the release of PRL from the pituitary gland. The serial measurement of estradiol may serve as an index of aromatization. Hyperprolactinemia in this setting is resistant to dopamine agonist therapy, as noted in multiple case reports. There are no established reference ranges for PRL levels for transgender patients on gender-affirming hormone therapy and no current guidelines regarding routine imaging or biochemical assessment during follow-up. Transgender patients with prolactinoma may require additional treatment with non-aromatizable androgens or the concomitant administration of aromatase inhibitors. Presentation: Friday, June 16, 2023

FRI330 A Rare Case Of Hypogonadotropic Hypogonadism In A Patient With Disseminated Tberculosis And Tuberculoma Involving Tuberculum Sellae

Abstract Disclosure: J.S. Genkil: None. S. Ahsun: None. N. Mohan: None. C. Anastasopoulou: None. Introduction: Central nervous system (CNS) tuberculosis accounts for 1-10% of all tuberculosis (TB) infections and has been known to lead to irreversible consequences. CNS TB may present variably as meningeal tuberculosis, tuberculoma, tuberculous abscess, hydrocephalus, ventricular involvement or cerebritis. Tuberculomas involving the sellar region are amongst the rarest of presentations. We describe a unique case of hypogonadotropic hypogonadism with CNS tuberculoma. Case: A 46-year-old male with depression, alcohol use, tobacco smoking, and daily K2 spice use presented to the hospital with multiple days of upper extremity weakness, seizures, and slurred speech. Head CT was done that showed a soft tissue density with mild hypoattenuation on the right frontal region. MRI of the brain showed 3 round 4-5mm lesions with rim enhancement in the frontal lobes. Chest CT showed apical lung lesion. It was believed that patient had a malignant process with metastasis to the brain. During his course, it was discovered that he had TB exposure from his mother several months ago. Despite multiple negative AFB sputum samples, left lung biopsy confirmed TB diagnosis. He was subsequently diagnosed with tubercular meningitis with tuberculomas, one of them involving tuberculum sellae. The patient was started on antitubercular treatment with isoniazid, rifampin, pyrazinamide, streptomycin, and dexamethasone. Lab revealed normal thyroid studies, but very low total testosterone&amp;lt;20 ng/dl (Normal 220-872 ng/dl), with low FSH=2.6 IU/L (Normal 1-12 IU/L) and LH=0.8 IU/ml (Normal 0.6-12.1 IU/ml), with normal prolactin=7.9 ug/L (Normal 3.5-19.4 ug/L). To treat hypogonadotropic hypogonadism, the patient was started on weekly testosterone supplementation with testosterone cypionate 50 mg subcutaneous injections. Ultimately the patient was discharged to a full-time nursing facility and made significant clinical and functional improvement. Discussion: TB of the CNS is among the least common of extra pulmonary tuberculosis yet is associated with the most devastating manifestations making it a feared complication of TB. These lesions are associated with high rates of morbidity and mortality despite appropriate therapy so prompt diagnosis is key. CNS tuberculomas may present isolated or in combination with pulmonary TB. They are unique as they may masquerade as other intracranial space occupying lesions such as tumors or hematomas, further complicating diagnosis. In particular, sellar and suprasellar region tuberculomas are rare and can present with varied amount of hypopituitarism. In the patient’s case, he developed hypogonadotropic hypogonadism which was successfully treated with testosterone replacement. Hypogonadotropic hypogonadism can only be recognized if there is a high index of suspicion and can result in improvement of the quality of life with preservation of sexual function. Presentation: Friday, June 16, 2023

THU576 Anabolic Androgenic Steroid Abuse In Cis-gender Female Bodybuilder

Abstract Disclosure: E.M. Niedzialkowska: None. D. Shelden: None. Introduction: Anabolic androgenic steroids (AAS) are used in bodybuilders to increase muscle mass. Abuse has surged as they are regarded as potent image enhancement drugs. There are a variety of illegal AAS available. Their true content is often unknown and dosing regimens frequently include concurrent use of multiple hormonally active agents. Use among female body builders is rarely reported. Having significantly lower levels of natural testosterone, females may be more susceptible to side effects and toxicity associated with AAS abuse. Clinical case: 36 year old cis-gender female presented to the Endocrinology clinic for evaluation of fatigue. The patient worked as a personal trainer at a gym and began participating in bodybuilding competitions. A year prior to the visit the patient was started on a steroid regimen by a friend at the gym. The patient’s regimen included testosterone cypionate (250mg-350mg a week) and trenbolone acetate. Anastozole was added to limit conversion to estrogen but was not administered on a regular basis. The patient reported no gender dysphoria. She has not had a menstrual period since she started the AAS. The patient was also diagnosed with acute kidney injury at the time of AAS initiation and further work up showed negative ANA, C3, C4, normal UA and protein/creatinine ratio. Her kidney injury was deemed to be related to NSAID and testosterone use. At the time of the visit laboratory results were significant for testosterone of &amp;gt;1500 ng/dl (N 240-1080), IGF-1 359 ng/ml (N 63-223), LH &amp;lt;0.1 mUI/ml (N&amp;gt;0.6), FSH &amp;lt;0.5 mUI/ml (N&amp;gt;1.4), estradiol 47 pg/ml (N 21-251), prolactin 10.8 ng/ml (N 3-30), hemoglobin 17.4 g/dl (N 12-15.1), platelets 416 bil/L (150-400), TSH 0.75 uIU/ml (N 0.4-4.5), creatinine 1.33 mg/dl (N 0.5-1.1), eGFR 53 ml/min/1.73m2. The patient's testosterone regimen was gradually decreased to 100 mg weekly with plans to further decrease the dose and with close follow up and monitoring of gonadotropins. Treatment to stimulate endogenous estrogen production may be necessary despite her current value being within normal limits as this may be a function of peripheral conversion of exogenous testosterone. Conclusion: AAS abuse is infrequent among cis-gender females. Its use in female bodybuilders increases muscle strength and athletic performance. Exogenous administration of synthetic testosterone results in negative feedback on the hypothalamic-pituitary axis, inhibiting GnRH, leading to inhibition of FSH and LH production leading to amenorrhea in females. AAS has also been associated with kidney injury with reports from animal studies suggesting testosterone induced podocyte damage and apoptosis. The steroid regimens used by bodybuilders differ and include multiple hormonally active agents. Its abuse among cis-gender women is uncommon and further research is needed to evaluate its toxicity among this group. Presentation Date: Thursday, June 15, 2023